“These results suggest that nivolumab should be considered a new standard of care for patients with previously treated MSI-H advanced CRC,” said lead study author Michael J. Overman, MD, associate professor, department of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center.

“This is in line with a recent amendment to the NCCN Guidelines which recommends that all metastatic colorectal cancer patients have testing for MSI-H, and that after initial therapy, those patients with MSI-H disease should be considered for pembrolizumab or nivolumab monotherapy,” added Overman.

The data Overman presented at the GI Symposium were for 74 MSI-H patients who received 3 mg/kg of nivolumab every 2 weeks. The primary endpoint was ORR, with additional outcome measures including PFS, OS, and safety.

For the 74-patient cohort, the median age was 52.5 years (range, 26-79), 59.5% of patients were male, and 87.8% of patients were white. All patients had an ECOG performance status of 0 or 1. The majority of patients (54.1%) had at least 3 prior lines of therapy.

A history of Lynch syndrome was reported for 31.1% of patients and 16.2% had BRAF mutations. Among the 66 patients for whom PD-L1 status was evaluable, 28.4% (n = 21) had PD-L1 expression ≥1%. The median number of doses was 13 (range 1-54), and forty patients (54.1%) remained on treatment.

The ORR by investigator assessment was 31.1% (95% CI, 20.8-42.9), comprising 23 partial responses. The stable disease rate was 39.2%, the progressive disease rate was 24.3%, and the response was not determinable for 5.4%. The disease control rate of ≥12 weeks was 68.9%.

Among the 23 investigator-assessed responders, the median time to response was 2.8 months, the median duration of response was not yet reached, and 83% (n = 19) of responses were ongoing.

The ORR by blinded independent review was 27% (95% CI, 17.4-38.6), comprising 2 complete responses and 18 partial responses. The stable disease rate was 37.8%, the progressive disease rate was 27% and the response was not determinable for 11.1%. The disease control rate of ≥12 weeks was 62.2%.

Overman noted that there was response and clinical benefit regardless of PD-L1 expression, BRAF mutation status, KRAS mutation status, and clinical history of Lynch Syndrome.

The rate of all-grade adverse events (AEs) was 68.9%, with the most common being fatigue (23%), diarrhea (21.6%), pruritus (13.5%), lipase increased (12.2%), and rash (10.8%). Grade 3/4 AEs occurred in 20.3% of patients, including lipase increased (8.1%), fatigue (1.4%), and diarrhea (1.4%).

Among the 45.9% of patients who discontinued treatment, the reasons included disease progression (36.5%), treatment-related toxicity (5.4%), maximum clinical benefit (1.4%), patient decision (1.4%) and withdrawn consent (1.4%). The were no deaths associated with treatment-related toxicity.